The absorptive and secretory processes which characterize epithelial tissues such as comprise much of the kidney and G.I. tract are incompletely understood, but must represent, fundamentally, the movement of substances across a single layer of epithelial cells. Evidence has accumulated to suggest that transepithelial ion movement may proceed via two parallel paths, one through the cells, and another circumventing the cells via paracellular shunt pathways. In addition, there is ample evidence that in order for such tissues to exhibit active transport of sodium or other ions, the cell membranes which constitute the functional boundaries of the epithelial cell layer must possess fundamentally different properties. The mechanisms and regulation of epithelial ion transport must, therefore, be understood in terms of the single cell membranes and paracellular paths which characterize these cell layers. The proposed studies will be directed toward characterizing the cellular and paracellular pathways for ion movement across a relatively simple epithelium, the turtle colon. A major portion of this effort will be an attempt to determine the properties of the single cell membranes at the mucosal and serosal boundaries of the cell layer. We will attempt to determine how normal agents, such as aldosterone, may act by modifying the properties of cell membranes. We will employ techniques which should enable us to separate transepithelial isotope fluxes into cellular and non-cellular components. In addition we will attempt to measure directly the entry of ions and lipophilic non-electrolytes across the mucosal and serosal membranes of the colon. A detailed consideration of the ion and nonelectrolyte selectivities of the cell membranes should provide information as to the "solvent properties" of these membranes and, hence, their composition. We will explore the effects of various agents which modify the properties of cell membranes. We will attempt to test directly the hypothesis that aldosterone acts by increasing the Na-permeability of the mucosal cell membrane. BIBLIOGRAPHIC REFERENCES: Dawson, D.C. and P.F. Curran. Sodium transport by the colon of Bufo marinus: Na uptake across the mucosal border. J. Membrane Biol. 28:295-307, (1976).